EP2635246A1 - Marked solid pharmaceutical form, and method for the production thereof by means of laser marking - Google Patents

Marked solid pharmaceutical form, and method for the production thereof by means of laser marking

Info

Publication number
EP2635246A1
EP2635246A1 EP11802465.2A EP11802465A EP2635246A1 EP 2635246 A1 EP2635246 A1 EP 2635246A1 EP 11802465 A EP11802465 A EP 11802465A EP 2635246 A1 EP2635246 A1 EP 2635246A1
Authority
EP
European Patent Office
Prior art keywords
laser
μηη
groove
pharmaceutical form
range
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP11802465.2A
Other languages
German (de)
French (fr)
Inventor
Sébastien DASSIE
Laurence Peiret
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi SA
Original Assignee
Sanofi SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi SA filed Critical Sanofi SA
Publication of EP2635246A1 publication Critical patent/EP2635246A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/007—Marking tablets or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J2205/00—General identification or selection means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41M—PRINTING, DUPLICATING, MARKING, OR COPYING PROCESSES; COLOUR PRINTING
    • B41M5/00—Duplicating or marking methods; Sheet materials for use therein
    • B41M5/24—Ablative recording, e.g. by burning marks; Spark recording
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
    • Y10T428/24355—Continuous and nonuniform or irregular surface on layer or component [e.g., roofing, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
    • Y10T428/24479—Structurally defined web or sheet [e.g., overall dimension, etc.] including variation in thickness

Definitions

  • the invention relates to a marked solid pharmaceutical form, and a laser marking method for producing this form.
  • Such laser marking is invisible to the naked eye, but can be revealed by light microscopy. It is a means of effective fight against counterfeiting.
  • Counterfeiters endanger the safety of the patient, who can be treated with a product that does not include any active ingredient and therefore has no beneficial effect. At worst, the patient may be treated with a product having adverse effects.
  • the suspect product can be authenticated for example by analysis of the composition of the product, but such an analysis is slow and expensive.
  • an authentic product can come from different sources, which complicates this detection.
  • the laser marking of pharmaceutical tablets is described in the document WO 2009/051794.
  • This network is intended to be revealed later by Moiré effect, during the superposition of a revealing layer.
  • the grating is made by ablation of a part of the surface that can be performed by laser.
  • the dimensions of the network are of the order of one micrometer, and in particular the depth of the ablation is between 50 nm and 5 micrometers ( ⁇ ).
  • the invention advantageously makes it possible to provide an effective solution to the fight against counterfeiting, and to overcome the disadvantages of the methods and devices of the prior art.
  • the invention makes it possible to propose an anti-counterfeiting solution that meets the needs of the pharmaceutical industry in terms of cost, efficiency, and ease of implementation, both in characterization and in detection.
  • one of the objects of the invention is a marked solid pharmaceutical form comprising at least one continuous groove marking its surface, said groove being of depth lying in a range from 10 ⁇ to 100 ⁇ , preferably from 20 ⁇ to 50 ⁇ . ⁇ .
  • the groove furthermore has a width in the range of from 5 ⁇ to 120 ⁇ , preferably from
  • the groove forms a closed continuous line.
  • the groove is preferably of length lying in the range 250 m to 3 mm, preferably 250 ⁇ to 500 ⁇ .
  • the surface of the pharmaceutical form has a mean depth of roughness in the range of 10 ⁇ to 40 ⁇ , preferably 20 ⁇ to 40 ⁇ .
  • the pharmaceutical form generally comprises at least two grooves each forming a closed continuous line.
  • the pharmaceutical form comprises at least two grooves, each groove being separated from another groove by a distance of at most 100 ⁇ .
  • the groove forms a marking pattern invisible to the naked eye, and not perceptible to the touch.
  • the groove is part of a side square comprised in a range of 100 ⁇ to 250 ⁇ , preferably from 200 ⁇ to 250 ⁇ .
  • the pharmaceutical form according to the invention is preferably selected from the group consisting of sticks, tablets, capsules, chewing gums and granules, preferably selected from the group consisting of tablets.
  • the invention also relates to a method for labeling at least one solid pharmaceutical form according to the invention, said method comprising the formation of at least one groove by ablation of the surface of the solid form by means of a laser beam, said method being such that laser ablation is performed with laser energy in the range of 0.1 mJ / mm 2 to 500 mJ / mm 2 , preferably in the range of 0.1 mJ / mm 2 to 250 mJ / mm 2 .
  • the marking method comprises providing a source of laser beam, providing means for optically guiding the laser beam to the surface of the shape, providing relative displacement means between the shape and the radius. laser, and producing a continuous groove on the surface of the shape by means of laser ablation by the laser beam and by means of the relative displacement of the surface and the laser beam.
  • the optical guiding means preferably comprise a focussing lens, focal length even more preferably selected from the group consisting of 50 mm, 60 mm and 100 mm.
  • the laser beam is of pulse duration from 100 fs to 50 ns and energy per pulse from 0.1 ⁇ to 100 ⁇ .
  • an infrared laser with a pulse duration of 100 to 1000 fs, energy per pulse of 0.1 ⁇ to 100 ⁇ , preferably of 0.1 ⁇ to 30 ⁇ , and of length waveform in the range of 1000 to
  • a laser with a wavelength of 1030 nm is used.
  • an ultraviolet laser of pulse duration of 5 to 50 ns, of energy per pulse of 1 to 100 ⁇ , preferably 3 ⁇ to 100 ⁇ , and of wavelength within a range of 10 to 380 nanometers.
  • a laser with a wavelength of 266 nm is used.
  • the laser guiding means comprise at least one means for separating the laser beam into a plurality of secondary rays so as to form, preferably simultaneously, several continuous grooves on the surface of the pharmaceutical form.
  • the invention finally relates to a packaging article comprising at least one pharmaceutical form according to the invention.
  • the pharmaceutical form is marked (or etched) by the groove (or incision).
  • the depth of the groove can be measured by atomic force microscopy, but such a measurement is difficult to perform.
  • the groove depth according to the invention is such that the groove does not cross a coating (or coating) of the pharmaceutical form.
  • the depth of groove measurement can be carried out by marking, according to a given parameterization, a film-coated, film-coated tablet, typically of thickness 50 ⁇ or 100 ⁇ . If the film has not been traversed by the marking, the groove depth is in one of the ranges according to the invention.
  • the marking thus parameterized can then be used on a naked tablet or on a film-coated tablet.
  • the width of the groove is measurable by scanning electron microscopy, the measurement accuracy being generally + or - 5%.
  • marking is performed by laser ablation, the characteristics of the laser beam and the marking conditions allow the skilled person, if he considers it necessary, to establish a link between the width of the groove and the depth of the groove .
  • pharmaceutical form (or “drug form” or “dosage form”) is meant according to the invention any form in which are put at least one active ingredient and at least one excipient (inactive material) to form a drug.
  • a medicine is a substance used to prevent and / or treat, usually treat, a disease. This pharmaceutical form generally corresponds to the final physical appearance of the drug as it will be used in a patient.
  • a pharmaceutical form is "solid” according to the invention, if it is limited by stable surfaces.
  • continuous is understood to mean a groove realized point by point, the points being sufficiently close together so that, in observation at the furrow scale, one has the impression of a continuous groove.
  • Each point is usually the result of laser ablation through a laser beam pulse. This advantageously makes it possible, in the context of the invention, to obtain the sharpness of the pattern created by the continuous groove or grooves. It would be possible to define the "continuous" groove by a maximum tolerance on the differences in groove depth: eg depth deviation of 5 to 20%, preferably 5 to 15%, over the entire length of the groove.
  • the pharmaceutical form of the invention is such that the dissolution profiles of the unlabeled pharmaceutical form and of the labeled pharmaceutical form are almost identical.
  • the marked dissolution profiles of a tablet are not modified with respect to the dissolution profile of the unlabeled tablet due to the marking operation.
  • the pharmaceutical form according to the invention is such that the groove forms a marking pattern invisible to the naked eye, and not perceptible to the touch.
  • invisible to the naked eye is meant according to the invention, not perceptible to human vision without technical assistance. This technical aid is typically a microscope. In general, an object of greater dimension less than about 100 ⁇ is considered invisible to the naked eye.
  • this marking makes it possible to distinguish said pharmaceutical form from counterfeit products by virtue of the use of an optical microscope, generally at a magnification of 20 or 100. This makes it possible to have a pharmaceutical form specially adapted to the fight anti-counterfeiting.
  • the furrow is in a side square within a range of 100 ⁇ to 250 ⁇ , preferably from 200 ⁇ to 250 ⁇ .
  • the skilled person is able to achieve the marking pattern so that the marking remains invisible to the naked eye, and not perceptible to the touch, for example taking into account the width of the groove and the size of the square in which the motif is inscribed.
  • the groove is generally located on a portion of the outer surface of the pharmaceutical form, this portion being accessible and, in particular, visible.
  • the location on the surface of the tablet of this part generally depends on the packaging in which may be present form. So, in the case the more usual of a substantially cylindrical compact of low height, the groove is preferably present on one of the surfaces of substantially circular shape, and not on the edge of this tablet.
  • the dimensions of the groove according to the invention imply that the marking pattern produced by the groove is advantageously clean and precise.
  • the pharmaceutical forms of the invention generally have a marking quality such that the marking pattern is not masked by the roughness of the surface of said shape.
  • the marking pattern has a particularly long life.
  • the groove preferably forms a closed continuous line.
  • the length of the groove is preferably in the range 250 ⁇ to 3 mm, preferably 250 ⁇ 500 ⁇ . Because of the possibility of making a groove of very small width, the skilled person can achieve, in these ranges of length, a groove invisible to the naked eye, even with a length of a few tenths to a few millimeters.
  • the surface of the pharmaceutical form has a mean depth of roughness in the range of 10 ⁇ to 40 ⁇ , preferably 20 ⁇ to 40 ⁇ .
  • the pharmaceutical form according to the invention may comprise a continuous groove as it is visible, under the conditions indicated above, even when the surface of the pharmaceutical form is very rough, ie with an average roughness depth of about 40 ⁇ . .
  • the average roughness depth (Rt) or average height of the roughness profile (Rz) is as defined in ISO 4287: 1998.
  • Rt is the arithmetic mean of the individual profile heights over the evaluation length.
  • Rz is the individual profile height which is, for a base length, the difference between the highest peak and the deepest hollow. According to the invention, five basic lengths are considered per evaluation length.
  • the pharmaceutical form comprises at least two grooves each forming a closed continuous line.
  • the pharmaceutical form comprises at least two grooves, each groove being separated from another groove by a distance of at most 100 ⁇ , for example included in a range of 10 m to 80 ⁇ .
  • a distance is the shortest distance separating any point of a groove from any other point in another groove.
  • the pharmaceutical form is generally selected from the group consisting of sticks, tablets, capsules, chewing gums and granules, preferably selected from the group consisting of tablets.
  • tablettes are meant according to the invention coated tablets (or film) or not, effervescent or not, gastroresistant or not, immediate release or prolonged (or modified), to swallow or to use in the oral cavity, possibly soluble or dispersible, orodispersible tablets or oral lyophilisates.
  • capsules is meant according to the invention soft-shell or hard-shell capsules (capsules), immediate release or prolonged (or modified), gastroresistant or not, and the tablets.
  • the reason for the marking on the pharmaceutical form according to the invention is, for example, an anti-counterfeit logo, a text, or any form that the marking tool can perform.
  • the invention also relates to a method for labeling at least one solid pharmaceutical form according to the invention, said method comprising the formation of at least one groove by ablation of the surface of the solid form by means of a laser beam, said method being such that laser ablation is performed with laser energy in the range of 0.1 mJ / mm 2 to 500 mJ / mm 2 , preferably in the range of 0.1 mJ / mm 2 to 250 mJ / mm 2 .
  • the marking process according to the invention is of great precision since it allows the pharmaceutical forms according to the invention to be produced by marking them with any anti-counterfeit type motif such as a logo. This marking process is also of great clarity since the grooves of these marked pharmaceutical forms are visible under optical microscopy, from a magnification of 20.
  • Such a marking method advantageously makes it possible to produce a marked pharmaceutical form according to the invention, the groove (s) being invisible to the eye naked and not perceptible to the touch, without modifying the pharmacological properties of said form.
  • the marking method comprises the provision of a laser beam source, the provision of optical guidance means for the laser beam up to the surface of the shape, the provision of relative displacement means between the shape and the laser beam, and producing a continuous groove on the surface of the form by means of laser ablation by the laser beam and by means of relative displacement of the surface and the laser beam.
  • the optical guiding means comprise a focusing lens, focal length preferably selected from the group consisting of 50 mm, 60 mm and 100 mm.
  • the laser beam (or beam) is of pulse duration from 100 fs to 50 ns and energy per pulse from 0.1 to 100 ⁇ .
  • the method is such that an infrared laser with a pulse duration of 100 to 1000 fs, energy per pulse of 0.1 to 100 ⁇ , preferably 0.1 to 100 ⁇ , is used. 30 ⁇ , and wavelength in the range of 1000 to 1,000 nanometers. In such a case, preferably, the laser has a wavelength of 1030 nm.
  • the method is such that an ultraviolet laser with a pulse duration of 5 to 50 ns, energy per pulse of 1 to
  • the laser has a wavelength of 266 nm.
  • the laser guiding means comprise at least one means for separating the laser beam into a plurality of secondary rays so as to form a plurality of continuous grooves on the surface of the solid pharmaceutical form. Preferably the formation of the multiple grooves takes place simultaneously.
  • FIG. 1 schematically represents an optical system forming part of a laser marking device according to the invention
  • FIG. 2 schematically represents the laser marking device according to the invention comprising the optical system of FIG. 1.
  • Figure 1 schematically shows an optical system 9 forming part of a laser marking device 1 according to the invention.
  • the optical system 9 consists of parts 2, 3, 4, 5, 6, 7 and 8.
  • a source 2 of laser beam emits a laser beam L which passes through the optical system 9.
  • the laser beam L passes through an h / 2 blade or half-wave plate, 3, creating a phase shift of 180 °, that is to say say a delay of half a wavelength, then a polarizer cube 4 to modify the energy per pulse, and a ⁇ / 4 blade or quarter wave plate, 5, to have a polarization circular need for good homogeneity of ablation on both axes of laser scanning.
  • a mirror 7 at 45 ° C then a mirror 7 at 45 ° C to a laser focussing piece 8 provided with a focusing lens (not shown) for targeting and concentration of the laser beam at the focal point.
  • Figure 2 illustrates the device 1 for marking the tablet C of Figure 1.
  • the device 1 comprises the optical system 9, and allows the marking of a tablet C by means of a targeted and entered laser beam 11, which is focused on the surface of the tablet C.
  • the system Optical 9 comprises the source, the optical elements and the focusing elements of the laser.
  • the tablet C is present in a cylindrical cavity 10 for positioning the tablet C in the laser field.
  • the cavity 10 belongs to an aluminum tool (not shown) having cavities, for example 14 cavities, all identical with a diameter of 9.5 mm and a depth of 6 mm. This tool is able to be closed hermetically for transport by a transparent plastic cover.
  • the relative movement of the surface of the tablet and the laser beam is here obtained by means of displacement of the tablet related to the tooling.
  • control and detection of these displacements are linked to a control device, for example managed by software, which also analyzes the parameters of the laser source.
  • the device 1 according to the invention was used to mark different tablets.
  • the verification of the marking pattern which comprises two continuous grooves closed next to each other, was carried out by optical microscope.
  • the labeling motif has been characterized by scanning electron microscopy (SEM).
  • SEM scanning electron microscopy
  • a dark pink film-coated tablet tablet C1, size LxWxH
  • a white oblong tablet tablet C3, size Lxlxh
  • the tests carried out consisted in marking the tablets by fixing the values of several parameters which are: the focal length of the focusing lens F (which corresponds to the diameter of the lens used), the energy per pulse E (linked to the power P and at the firing rate v), the scanning speed (speed of movement of the beam on the laser), and the wavelength ⁇ . All these settings of the laser beam can be summarized in a single parameter which is the energy per area.
  • the purpose of these marking tests was to obtain, for each tablet, an anti-counterfeit marking invisible to the naked eye, not perceptible to the touch and visible under the microscope. The results of the various tests are summarized below.
  • laser S-Pulse HP 2 Amplitude Systems
  • Quadrupled Vanadate laser named Laser III.
  • Pulse duration 500 fs
  • Pulse energy used 1 - 100 ⁇
  • Pulse duration 500 fs
  • Lenses used Lens f-theta 50mm; Afocal x3
  • a first marking test of a C1 tablet was performed with the laser I and a focal length of 60 mm.
  • the laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ.
  • the scanning speed of the C1 surface was 2000 mm / s.
  • the energy per area was 1 mJ / mm2.
  • This test was carried out on a pattern comprising two closed grooves separated from one another, an elliptical-like groove and a groove of roughly elliptical type.
  • the shortest distance between these two furrows was about 10 ⁇ .
  • the pattern was of size 100 x 90 ⁇ . This motif was invisible to the naked eye. By optical microscopy with an enlargement of 100, it was possible to visualize this pattern.
  • the filming had a thickness of 50 ⁇ . After removal of the film coating after the test, by cutting the tablet with a microtome which made it possible to drop the film, it was possible to observe by scanning electron microscopy the integrity of the tablet and to check that the groove made by laser marking had not passed through the film coating layer.
  • the laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ.
  • the scanning speed of the C1 surface was 25 mm / sec.
  • the energy per surface was 240 mJ / mm 2 .
  • a complete pattern size 190 x 150 ⁇ was engraved, as in Example 1A.
  • a first marking test of a C2 tablet was performed with the laser I and a focal length of 60 mm.
  • the laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ.
  • the scanning speed of the surface of C1 was 200 mm / s.
  • the energy per area was 5 mJ / mm 2.
  • a complete pattern of size 200 x 180 ⁇ has been engraved, as in the example
  • a second marking test of a C2 tablet was performed with the laser III and a focal length of 50 mm.
  • the laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ.
  • the scanning speed of the C1 surface was 25 mm / sec.
  • the energy per surface was 240 mJ / mm 2.
  • a complete pattern of size 190 x 150 ⁇ has been engraved, as in the example
  • EXAMPLE 3 White uncoated (C3) white tablet Example 3A.
  • a first marking test of a C3 tablet was performed with the laser III and a focal length of 50 mm.
  • the laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ.
  • the scanning speed of the C1 surface was 50 mm / sec.
  • the area energy was 120 mJ / mm 2.
  • the complete engraved pattern was 190 x 150 ⁇ , as in Example 1A.
  • the laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ.
  • the scanning speed of the C1 surface was 200 mm / sec.
  • the energy per area was 2.5 mJ / mm2.
  • the complete engraved pattern was of size 200 x 180 ⁇ , as in Example 1A.
  • the average marking time is about 80 ms.
  • This average marking time generally includes the time due to the processing of the information by the marking software and the time due to the marking itself. This could easily be optimized within the scope of the invention by using software dedicated to a particular pattern or by multiplying the number of laser beams by an optical system that multiplies the initial beam.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Thermal Transfer Or Thermal Recording In General (AREA)
  • Laser Beam Processing (AREA)

Abstract

The invention relates to a marked solid pharmaceutical form including a continuous groove on the surface thereof, said groove preferably being 20 µm to 50 µm deep and preferably 5 µm to 120 µm wide. The invention also relates to a method for marking such a pharmaceutical form by forming at least one groove therein by means of laser ablation of the surface of the solid form, said method being such that the laser ablation is carried out with laser energy of 0.1 to 500 mJ/mm2.

Description

Forme pharmaceutique solide marquée et son procédé de  Strong labeled pharmaceutical form and its method of
DOMAINE DE L'INVENTION FIELD OF THE INVENTION
L'invention concerne une forme pharmaceutique solide marquée, et un procédé de marquage laser permettant de réaliser cette forme. Un tel marquage laser est invisible à l'œil nu, mais peut être révélé par microscopie optique. C'est un moyen de lutte efficace contre la contrefaçon.  The invention relates to a marked solid pharmaceutical form, and a laser marking method for producing this form. Such laser marking is invisible to the naked eye, but can be revealed by light microscopy. It is a means of effective fight against counterfeiting.
Dans la suite, le mot « marquage » désignera à la fois le marquage en lui- même et le « procédé de marquage ».  In the following, the word "marking" will designate both the marking itself and the "marking process".
ART ANTERIEUR ET PROBLEME TECHNIQUE  PRIOR ART AND TECHNICAL PROBLEM
La lutte contre la contrefaçon est un problème majeur de l'industrie pharmaceutique. En effet, la contrefaçon est le plus grand type de fraude observé dans cette industrie.  The fight against counterfeiting is a major problem for the pharmaceutical industry. Indeed, counterfeiting is the largest type of fraud observed in this industry.
Les contrefacteurs mettent en péril la sécurité du patient, qui peut être traité par un produit ne comprenant aucun principe actif et n'ayant donc aucun effet bénéfique. Au pire, le patient peut être traité par un produit ayant des effets néfastes.  Counterfeiters endanger the safety of the patient, who can be treated with a product that does not include any active ingredient and therefore has no beneficial effect. At worst, the patient may be treated with a product having adverse effects.
Dans tous ces cas de fraudes de produits pharmaceutiques, la détection des produits suspects est essentielle. Le produit suspect peut être authentifié par exemple par analyse de la composition du produit, mais une telle analyse est lente et chère. De plus, un produit authentique peut provenir de différentes sources, ce qui complique cette détection.  In all these cases of pharmaceutical fraud, the detection of suspect products is essential. The suspect product can be authenticated for example by analysis of the composition of the product, but such an analysis is slow and expensive. In addition, an authentic product can come from different sources, which complicates this detection.
De nombreuses méthodes de lutte anti-contrefaçon ont été envisagées dans l'art antérieur. Ainsi, des méthodes d'impression, par exemple sur les emballages ou « blisters » (ou « emballages coques »), ou des méthodes de caractérisations telles que des codes barres, existent. Néanmoins, parmi les nombreuses solutions pour lesquelles des investigations ont été menées, il ne ressort aucun consensus de lutte anti-contrefaçon car aucune de ces solutions ne remplit tous les critères de coût, d'efficacité, et de facilité de mise en œuvre, à la fois dans la caractérisation et dans la détection.  Many anti-counterfeiting methods have been contemplated in the prior art. Thus, printing methods, for example on packaging or "blister packs", or characterization methods such as barcodes, exist. Nevertheless, among the many solutions for which investigations have been carried out, there is no consensus on the fight against counterfeiting because none of these solutions meets all the criteria of cost, efficiency, and ease of implementation. both in characterization and in detection.
L'utilisation de laser a été envisagée dans le cadre de cette lutte anticontrefaçon dans l'industrie pharmaceutique, en particulier pour réaliser des motifs de marquage sur les surfaces des produits ou dispositifs médicaux en verre ou en matières plastiques, le plus souvent en polymère(s). The use of lasers has been envisaged as part of this fight against counterfeiting in the pharmaceutical industry, in particular to achieve marking patterns on the surfaces of medical products or devices made of glass or plastics, most commonly of polymer (s).
Dans ce cadre, le marquage par laser de comprimés pharmaceutiques est décrit dans le document WO 2009/051794. Celui-ci divulgue un comprimé à la surface duquel est formé un réseau. Ce réseau est destiné à être révélé ultérieurement par effet Moiré, lors de la superposition d'une couche révélatrice. Le réseau est réalisé par ablation d'une partie de la surface qui peut être effectué par laser. Les dimensions du réseau sont de l'ordre du micromètre, et en particulier la profondeur de l'ablation est entre 50 nm et 5 micromètres (μηη).  In this context, the laser marking of pharmaceutical tablets is described in the document WO 2009/051794. This discloses a tablet on the surface of which is formed a network. This network is intended to be revealed later by Moiré effect, during the superposition of a revealing layer. The grating is made by ablation of a part of the surface that can be performed by laser. The dimensions of the network are of the order of one micrometer, and in particular the depth of the ablation is between 50 nm and 5 micrometers (μηη).
Dans le cadre de l'industrie pharmaceutique, il existe donc à ce jour un besoin de disposer de formes pharmaceutiques solides dont chaque unité possède un moyen discret de reconnaissance anti-contrefaçon.  In the context of the pharmaceutical industry, therefore, there is a need to date for solid pharmaceutical forms, each unit of which has a discrete means of recognizing anti-counterfeiting.
L'invention permet avantageusement d'apporter une solution efficace à la lutte anti-contrefaçon, et de pallier les inconvénients des procédés et dispositifs de l'art antérieur. En particulier l'invention permet de proposer une solution de lutte anticontrefaçon qui répond aux besoins de l'industrie pharmaceutique en termes de coût, d'efficacité, et de facilité de mise en œuvre, à la fois dans la caractérisation et dans la détection.  The invention advantageously makes it possible to provide an effective solution to the fight against counterfeiting, and to overcome the disadvantages of the methods and devices of the prior art. In particular, the invention makes it possible to propose an anti-counterfeiting solution that meets the needs of the pharmaceutical industry in terms of cost, efficiency, and ease of implementation, both in characterization and in detection.
RESUME DE L'INVENTION  SUMMARY OF THE INVENTION
A cet effet, un des objets de l'invention est une forme pharmaceutique solide marquée comprenant au moins un sillon continu marquant sa surface, ledit sillon étant de profondeur comprise dans une fourchette de 10 μηη à 100 μηη, de préférence de 20 μηη à 50 μηι.  For this purpose, one of the objects of the invention is a marked solid pharmaceutical form comprising at least one continuous groove marking its surface, said groove being of depth lying in a range from 10 μηη to 100 μηη, preferably from 20 μηη to 50 μηη. μηι.
Selon un mode de réalisation préféré de l'invention, le sillon présente en outre une largeur comprise dans une fourchette de 5 μηη à 120 μηη, de préférence de According to a preferred embodiment of the invention, the groove furthermore has a width in the range of from 5 μηη to 120 μηη, preferably from
10 μηη à 100 μηη. 10 μηη at 100 μηη.
De préférence, le sillon forme une ligne continue fermée.  Preferably, the groove forms a closed continuous line.
Le sillon est de préférence de longueur comprise dans une fourchette de 250 m à 3 mm, de préférence de 250 μηη à 500 μηι.  The groove is preferably of length lying in the range 250 m to 3 mm, preferably 250 μηη to 500 μηι.
Selon une variante de l'invention, la surface de la forme pharmaceutique a une profondeur de rugosité moyenne comprise dans une fourchette de 10 μηη à 40 μηι, de préférence de 20 μηη à 40 μηι.  According to a variant of the invention, the surface of the pharmaceutical form has a mean depth of roughness in the range of 10 μηη to 40 μηι, preferably 20 μηη to 40 μηι.
Selon un mode de réalisation, la forme pharmaceutique comprend le plus souvent au moins deux sillons formant chacun une ligne continue fermée. Selon un autre mode de réalisation, indépendant ou non du mode de réalisation précédent, la forme pharmaceutique comprend au moins deux sillons, chaque sillon étant séparé d'un autre sillon d'une distance d'au plus 100 μηη. According to one embodiment, the pharmaceutical form generally comprises at least two grooves each forming a closed continuous line. According to another embodiment, independent or not of the previous embodiment, the pharmaceutical form comprises at least two grooves, each groove being separated from another groove by a distance of at most 100 μηη.
De façon préférée, le sillon forme un motif de marquage invisible à l'œil nu, et non perceptible au toucher.  Preferably, the groove forms a marking pattern invisible to the naked eye, and not perceptible to the touch.
Selon une variante, le sillon s'inscrit dans un carré de côté compris dans une fourchette de 100 μηη à 250 μηι, de préférence de 200 μηη à 250 μηι.  According to one variant, the groove is part of a side square comprised in a range of 100 μηη to 250 μηι, preferably from 200 μηη to 250 μηι.
La forme pharmaceutique selon l'invention est, de préférence, choisie dans le groupe formé par les bâtons, les comprimés, les capsules, les gommes à mâcher et les granulés, de préférence choisie dans le groupe formé par les comprimés.  The pharmaceutical form according to the invention is preferably selected from the group consisting of sticks, tablets, capsules, chewing gums and granules, preferably selected from the group consisting of tablets.
L'invention concerne aussi un procédé de marquage d'au moins une forme pharmaceutique solide selon l'invention, ledit procédé comprenant la formation d'au moins un sillon par ablation de la surface de la forme solide au moyen d'un rayon laser, ledit procédé étant tel que l'ablation laser est effectuée avec une énergie laser comprise dans une fourchette de 0,1 mJ/mm2 à 500 mJ/mm2, de préférence dans une fourchette de 0,1 mJ/mm2 à 250 mJ/mm2. The invention also relates to a method for labeling at least one solid pharmaceutical form according to the invention, said method comprising the formation of at least one groove by ablation of the surface of the solid form by means of a laser beam, said method being such that laser ablation is performed with laser energy in the range of 0.1 mJ / mm 2 to 500 mJ / mm 2 , preferably in the range of 0.1 mJ / mm 2 to 250 mJ / mm 2 .
De préférence, le procédé de marquage comprend la fourniture d'une source de rayon laser, la fourniture de moyens de guidage optique du rayon laser jusqu'à la surface de la forme, la fourniture de moyens de déplacement relatif entre la forme et le rayon laser, et la réalisation d'un sillon continu en surface de la forme au moyen d'ablation laser par le rayon laser et au moyen du déplacement relatif de la surface et du rayon laser.  Preferably, the marking method comprises providing a source of laser beam, providing means for optically guiding the laser beam to the surface of the shape, providing relative displacement means between the shape and the radius. laser, and producing a continuous groove on the surface of the shape by means of laser ablation by the laser beam and by means of the relative displacement of the surface and the laser beam.
Les moyens de guidage optique comprennent de préférence une lentille de focalisation, de focale de façon encore plus préférée choisie dans le groupe formé par 50 mm, 60 mm et 100 mm.  The optical guiding means preferably comprise a focussing lens, focal length even more preferably selected from the group consisting of 50 mm, 60 mm and 100 mm.
Le plus souvent, le rayon laser est de durée d'impulsion de 100 fs à 50 ns et d'énergie par impulsion de 0,1 μύ à 100 μύ.  Most often, the laser beam is of pulse duration from 100 fs to 50 ns and energy per pulse from 0.1 μύ to 100 μύ.
Selon l'invention, on peut utiliser un laser infrarouge de durée d'impulsion de 100 à 1000 fs, d'énergie par impulsion de 0,1 μύ à 100 μύ, de préférence de 0,1 μύ à 30 μύ, et de longueur d'onde comprise dans une fourchette de 1000 à According to the invention, it is possible to use an infrared laser with a pulse duration of 100 to 1000 fs, energy per pulse of 0.1 μύ to 100 μύ, preferably of 0.1 μύ to 30 μύ, and of length waveform in the range of 1000 to
1000000 nanomètres. Par exemple on utilise un laser de longueur d'onde de 1030 nm. 1000000 nanometers. For example, a laser with a wavelength of 1030 nm is used.
Selon l'invention, on peut utiliser un laser ultraviolet de durée d'impulsion de 5 à 50 ns, d'énergie par impulsion de 1 à 100 μύ, de préférence 3 μύ à 100 μύ, et de longueur d'onde comprise dans une fourchette de 10 à 380 nanomètres. Par exemple on utilise un laser de longueur d'onde de 266 nm. According to the invention, it is possible to use an ultraviolet laser of pulse duration of 5 to 50 ns, of energy per pulse of 1 to 100 μύ, preferably 3 μύ to 100 μύ, and of wavelength within a range of 10 to 380 nanometers. For example, a laser with a wavelength of 266 nm is used.
Le plus souvent, les moyens de guidage laser comprennent au moins un moyen de séparation du rayon laser en plusieurs rayons secondaires de façon à former, de préférence de façon simultanée, plusieurs sillons continus à la surface de la forme pharmaceutique.  Most often, the laser guiding means comprise at least one means for separating the laser beam into a plurality of secondary rays so as to form, preferably simultaneously, several continuous grooves on the surface of the pharmaceutical form.
L'invention concerne enfin un article de conditionnement comprenant au moins une forme pharmaceutique selon l'invention.  The invention finally relates to a packaging article comprising at least one pharmaceutical form according to the invention.
EXPOSE DETAILLE DES MODES DE REALISATION  DETAILED DESCRIPTION OF THE EMBODIMENTS
La forme pharmaceutique est marquée (ou gravée) par le sillon (ou incision). The pharmaceutical form is marked (or etched) by the groove (or incision).
La profondeur du sillon peut être mesurée par microscopie à force atomique, mais une telle mesure est délicate à effectuer. Ainsi, dans le cadre de l'invention, il a été jugé préférable, et plus simple, d'adopter une technique de mesure comparative. En effet, la profondeur de sillon selon l'invention est telle que le sillon ne traverse pas un pelliculage (ou enrobage) de la forme pharmaceutique.The depth of the groove can be measured by atomic force microscopy, but such a measurement is difficult to perform. Thus, in the context of the invention, it has been found preferable and simpler to adopt a comparative measurement technique. Indeed, the groove depth according to the invention is such that the groove does not cross a coating (or coating) of the pharmaceutical form.
Par suite, la mesure de profondeur de sillon peut s'effectuer par marquage, selon un paramétrage donné, d'un comprimé pelliculé, à pelliculage donné, typiquement d'épaisseur 50 μηη ou 100 μηι. Si le pelliculage n'a pas été traversé par le marquage, la profondeur de sillon est dans une des gammes selon l'invention. Le marquage ainsi paramétré peut ensuite être utilisé sur comprimé nu ou sur comprimé pelliculé. As a result, the depth of groove measurement can be carried out by marking, according to a given parameterization, a film-coated, film-coated tablet, typically of thickness 50 μηη or 100 μηι. If the film has not been traversed by the marking, the groove depth is in one of the ranges according to the invention. The marking thus parameterized can then be used on a naked tablet or on a film-coated tablet.
La largeur du sillon est mesurable par microscopie électronique à balayage, la précision de mesure étant généralement de + ou - 5%. Lorsque le marquage est réalisé par ablation laser, les caractéristiques du faisceau laser et les conditions de marquage permettent à l'homme du métier, s'il l'estime nécessaire, d'établir un lien entre la largeur du sillon et la profondeur du sillon.  The width of the groove is measurable by scanning electron microscopy, the measurement accuracy being generally + or - 5%. When marking is performed by laser ablation, the characteristics of the laser beam and the marking conditions allow the skilled person, if he considers it necessary, to establish a link between the width of the groove and the depth of the groove .
Par « forme pharmaceutique » (ou « forme médicamenteuse » ou « forme galénique »), on entend selon l'invention toute forme sous laquelle sont mis au moins un principe actif et au moins un excipient (matière inactive) pour former un médicament. Un médicament est une substance utilisée pour prévenir et/ou traiter, généralement traiter, une maladie. Cette forme pharmaceutique correspond généralement à l'aspect physique final du médicament tel qu'il sera utilisé chez un patient. Une forme pharmaceutique est « solide » selon l'invention, si elle est limitée par des surfaces stables. Par sillon « continu », on entend selon l'invention un sillon réalisé point par point, les points étant suffisamment rapprochés pour que, en observation à l'échelle du sillon, on ait l'impression d'un sillon continu. Chaque point est généralement le résultat d'une ablation laser grâce à une impulsion de rayon laser. Cela permet avantageusement, dans le cadre de l'invention, d'obtenir la netteté du motif créé par le ou les sillons continus. Il serait possible de définir le sillon « continu » par une tolérance maximale sur les différences de profondeur du sillon : e.g. écart de profondeur de 5 à 20%, de préférence de 5 à 15%, sur toute la longueur du sillon. By "pharmaceutical form" (or "drug form" or "dosage form") is meant according to the invention any form in which are put at least one active ingredient and at least one excipient (inactive material) to form a drug. A medicine is a substance used to prevent and / or treat, usually treat, a disease. This pharmaceutical form generally corresponds to the final physical appearance of the drug as it will be used in a patient. A pharmaceutical form is "solid" according to the invention, if it is limited by stable surfaces. According to the invention, the term "continuous" groove is understood to mean a groove realized point by point, the points being sufficiently close together so that, in observation at the furrow scale, one has the impression of a continuous groove. Each point is usually the result of laser ablation through a laser beam pulse. This advantageously makes it possible, in the context of the invention, to obtain the sharpness of the pattern created by the continuous groove or grooves. It would be possible to define the "continuous" groove by a maximum tolerance on the differences in groove depth: eg depth deviation of 5 to 20%, preferably 5 to 15%, over the entire length of the groove.
Avantageusement, la forme pharmaceutique de l'invention est telle que les profils de dissolution de la forme pharmaceutique non marquée et de la forme pharmaceutique marquée sont quasiment identiques. De ce fait, les profils de dissolution d'un comprimé marqués ne sont pas modifiés par rapport au profil de dissolution du comprimé non marqué du fait de l'opération de marquage.  Advantageously, the pharmaceutical form of the invention is such that the dissolution profiles of the unlabeled pharmaceutical form and of the labeled pharmaceutical form are almost identical. As a result, the marked dissolution profiles of a tablet are not modified with respect to the dissolution profile of the unlabeled tablet due to the marking operation.
Selon un mode de réalisation préféré de l'invention, la forme pharmaceutique selon l'invention est telle que le sillon forme un motif de marquage invisible à l'œil nu, et non perceptible au toucher. Par « invisible à l'œil nu » on entend selon l'invention, non perceptible à la vision humaine sans aide technique. Cette aide technique est typiquement un microscope. En général, un objet de plus grande dimension inférieure à environ 100 μηη est considéré comme invisible à l'œil nu. According to a preferred embodiment of the invention, the pharmaceutical form according to the invention is such that the groove forms a marking pattern invisible to the naked eye, and not perceptible to the touch. By "invisible to the naked eye" is meant according to the invention, not perceptible to human vision without technical assistance. This technical aid is typically a microscope. In general, an object of greater dimension less than about 100 μηη is considered invisible to the naked eye.
De ce fait, ce marquage permet de distinguer ladite forme pharmaceutique de produits contrefaisants grâce à l'utilisation d'un microscope optique, généralement sous un grossissement de 20 ou de 100. Cela permet de disposer d'une forme pharmaceutique spécialement adaptée à la lutte anti-contrefaçon. As a result, this marking makes it possible to distinguish said pharmaceutical form from counterfeit products by virtue of the use of an optical microscope, generally at a magnification of 20 or 100. This makes it possible to have a pharmaceutical form specially adapted to the fight anti-counterfeiting.
En général, le sillon s'inscrit dans un carré de côté compris dans une fourchette de 100 μηη à 250 μηη, de préférence de 200 μηη à 250 μηη. L'homme du métier est à même de réaliser le motif de marquage de façon à ce que le marquage reste invisible à l'œil nu, et non perceptible au toucher, par exemple en tenant compte de la largeur du sillon et de la taille du carré dans lequel s'inscrit le motif.  In general, the furrow is in a side square within a range of 100 μηη to 250 μηη, preferably from 200 μηη to 250 μηη. The skilled person is able to achieve the marking pattern so that the marking remains invisible to the naked eye, and not perceptible to the touch, for example taking into account the width of the groove and the size of the square in which the motif is inscribed.
Le sillon est généralement situé sur une partie de la surface extérieure de la forme pharmaceutique, cette partie étant accessible et, en particulier, visible. La localisation, sur la surface du comprimé, de cette partie dépend généralement du conditionnement dans lequel peut être présente ladite forme. Ainsi, dans le cas le plus usuel d'un comprimé sensiblement cylindrique de faible hauteur, le sillon est de préférence présent sur une des surfaces de forme sensiblement circulaire, et non sur la tranche de ce comprimé. The groove is generally located on a portion of the outer surface of the pharmaceutical form, this portion being accessible and, in particular, visible. The location on the surface of the tablet of this part generally depends on the packaging in which may be present form. So, in the case the more usual of a substantially cylindrical compact of low height, the groove is preferably present on one of the surfaces of substantially circular shape, and not on the edge of this tablet.
Il peut aussi être envisagé, de marquer la forme pharmaceutique par un motif de marquage visible à l'œil nu, qui permet de repérer l'endroit où se trouve le sillon invisible à l'œil nu, selon un ou des critères particuliers. Cela peut permettre au douanier d'avoir accès plus facilement au sillon, par microscopie optique, selon le ou les critères qui lui auront été fourni(s) par le fabricant de la forme pharmaceutique.  It may also be envisaged to mark the pharmaceutical form with a marking pattern visible to the naked eye, which makes it possible to locate the location of the groove invisible to the naked eye, according to one or more particular criteria. This may allow the customs officer to have easier access to the groove, by optical microscopy, according to the criteria or criteria that will have been provided by the manufacturer of the pharmaceutical form.
Les dimensions du sillon selon l'invention impliquent que le motif de marquage réalisé par le sillon est avantageusement net et précis. En particulier, les formes pharmaceutiques de l'invention présentent généralement une qualité de marquage telle que le motif de marquage n'est pas masqué par la rugosité de la surface de ladite forme. De plus, le motif de marquage a une durée de vie particulièrement longue.  The dimensions of the groove according to the invention imply that the marking pattern produced by the groove is advantageously clean and precise. In particular, the pharmaceutical forms of the invention generally have a marking quality such that the marking pattern is not masked by the roughness of the surface of said shape. In addition, the marking pattern has a particularly long life.
Le sillon forme de préférence une ligne continue fermée.  The groove preferably forms a closed continuous line.
La longueur du sillon est, de façon préférée, comprise dans une fourchette de 250 μηη à 3 mm, de préférence de 250 μηη à 500 μηι. Du fait de la possibilité de réaliser un sillon de très petite largeur, l'homme du métier peut réaliser, dans ces plages de longueur, un sillon invisible à l'œil nu, même avec une longueur de quelques dixièmes à quelques millimètres.  The length of the groove is preferably in the range 250 μηη to 3 mm, preferably 250 μηη 500 μηι. Because of the possibility of making a groove of very small width, the skilled person can achieve, in these ranges of length, a groove invisible to the naked eye, even with a length of a few tenths to a few millimeters.
Le plus souvent, la surface de la forme pharmaceutique a une profondeur de rugosité moyenne comprise dans une fourchette de 10 μηη à 40 μηη, de préférence de 20 μηη à 40 μηι.  Most often, the surface of the pharmaceutical form has a mean depth of roughness in the range of 10 μηη to 40 μηη, preferably 20 μηη to 40 μηι.
Avantageusement, la forme pharmaceutique selon l'invention peut comporter un sillon continu tel qu'il est visible, dans les conditions indiquées précédemment, même quand la surface de la forme pharmaceutique est très rugueuse, i.e. de profondeur de rugosité moyenne d'environ 40 μηη.  Advantageously, the pharmaceutical form according to the invention may comprise a continuous groove as it is visible, under the conditions indicated above, even when the surface of the pharmaceutical form is very rough, ie with an average roughness depth of about 40 μηη. .
La profondeur de rugosité moyenne (Rt) ou hauteur moyenne du profil de rugosité (Rz) est telle que définie dans la norme ISO 4287 :1998. Rt correspond à la moyenne arithmétique des hauteurs individuelles de profil sur la longueur d'évaluation. Rz correspond à la hauteur individuelle de profil qui est, pour une longueur de base, la différence entre le plus haut pic et le creux le plus profond. On considère selon l'invention cinq longueurs de base par longueur d'évaluation. Selon une variante de l'invention, la forme pharmaceutique comprend au moins deux sillons formant chacun une ligne continue fermée. The average roughness depth (Rt) or average height of the roughness profile (Rz) is as defined in ISO 4287: 1998. Rt is the arithmetic mean of the individual profile heights over the evaluation length. Rz is the individual profile height which is, for a base length, the difference between the highest peak and the deepest hollow. According to the invention, five basic lengths are considered per evaluation length. According to a variant of the invention, the pharmaceutical form comprises at least two grooves each forming a closed continuous line.
Selon une autre variante de l'invention, indépendante ou non de la variante précédente, la forme pharmaceutique comprend au moins deux sillons, chaque sillon étant séparé d'un autre sillon d'une distance d'au plus 100 μηη, par exemple comprise dans une fourchette de 10 m à 80 μηη. Une telle distance est la distance la plus courte séparant tout point d'un sillon de tout autre point d'un autre sillon.  According to another variant of the invention, independent or not of the preceding variant, the pharmaceutical form comprises at least two grooves, each groove being separated from another groove by a distance of at most 100 μηη, for example included in a range of 10 m to 80 μηη. Such a distance is the shortest distance separating any point of a groove from any other point in another groove.
La forme pharmaceutique est généralement choisie dans le groupe formé par les bâtons, les comprimés, les capsules, les gommes à mâcher et les granulés, de préférence choisie dans le groupe formé par les comprimés.  The pharmaceutical form is generally selected from the group consisting of sticks, tablets, capsules, chewing gums and granules, preferably selected from the group consisting of tablets.
Par « comprimés » on entend selon l'invention des comprimés enrobés (ou pelliculés) ou non, effervescents ou non, gastrorésistants ou non, à libération immédiate ou prolongée (ou modifiée), à avaler ou à utiliser dans la cavité buccale, éventuellement solubles ou dispersibles, les comprimés orodispersibles ou les lyophilisats oraux. Par « capsules » on entend selon l'invention des capsules à enveloppe molle ou à enveloppe dure (gélules), à libération immédiate ou prolongée (ou modifiée), gastrorésistante ou non, ainsi que les cachets.  By "tablets" is meant according to the invention coated tablets (or film) or not, effervescent or not, gastroresistant or not, immediate release or prolonged (or modified), to swallow or to use in the oral cavity, possibly soluble or dispersible, orodispersible tablets or oral lyophilisates. By "capsules" is meant according to the invention soft-shell or hard-shell capsules (capsules), immediate release or prolonged (or modified), gastroresistant or not, and the tablets.
Le motif du marquage sur la forme pharmaceutique selon l'invention est par exemple un logo anti-contrefaçon, un texte, ou toute forme que peut réaliser l'outil de marquage.  The reason for the marking on the pharmaceutical form according to the invention is, for example, an anti-counterfeit logo, a text, or any form that the marking tool can perform.
L'invention concerne aussi un procédé de marquage d'au moins une forme pharmaceutique solide selon l'invention, ledit procédé comprenant la formation d'au moins un sillon par ablation de la surface de la forme solide au moyen d'un rayon laser, ledit procédé étant tel que l'ablation laser est effectuée avec une énergie laser comprise dans une fourchette de 0,1 mJ/mm2 à 500 mJ/mm2, de préférence dans une fourchette de 0,1 mJ/mm2 à 250 mJ/mm2. The invention also relates to a method for labeling at least one solid pharmaceutical form according to the invention, said method comprising the formation of at least one groove by ablation of the surface of the solid form by means of a laser beam, said method being such that laser ablation is performed with laser energy in the range of 0.1 mJ / mm 2 to 500 mJ / mm 2 , preferably in the range of 0.1 mJ / mm 2 to 250 mJ / mm 2 .
Le procédé de marquage selon l'invention est d'une grande précision puisqu'il permet de réaliser les formes pharmaceutiques selon l'invention, en les marquant de tout motif de type anti-contrefaçon tel qu'un logo. Ce procédé de marquage est aussi d'une grande netteté puisque les sillons de ces formes pharmaceutiques marquées sont visibles en microscopie optique, à partir d'un grossissement de 20.  The marking process according to the invention is of great precision since it allows the pharmaceutical forms according to the invention to be produced by marking them with any anti-counterfeit type motif such as a logo. This marking process is also of great clarity since the grooves of these marked pharmaceutical forms are visible under optical microscopy, from a magnification of 20.
Un tel procédé de marquage permet avantageusement de réaliser une forme pharmaceutique marquée selon l'invention, le(s) sillon(s) étant invisible(s) à l'œil nu et non perceptible au toucher, sans modifier les propriétés pharmacologiques de ladite forme. Such a marking method advantageously makes it possible to produce a marked pharmaceutical form according to the invention, the groove (s) being invisible to the eye naked and not perceptible to the touch, without modifying the pharmacological properties of said form.
Selon une variante, le procédé de marquage comprend la fourniture d'une source de rayon laser, la fourniture de moyens de guidage optique du rayon laser jusqu'à la surface de la forme, la fourniture de moyens de déplacement relatif entre la forme et le rayon laser, et la réalisation d'un sillon continu en surface de la forme au moyen d'ablation laser par le rayon laser et au moyen de déplacement relatif de la surface et du rayon laser.  According to one variant, the marking method comprises the provision of a laser beam source, the provision of optical guidance means for the laser beam up to the surface of the shape, the provision of relative displacement means between the shape and the laser beam, and producing a continuous groove on the surface of the form by means of laser ablation by the laser beam and by means of relative displacement of the surface and the laser beam.
En général, les moyens de guidage optique comprennent une lentille de focalisation, de focale de préférence choisie dans le groupe formé par 50 mm, 60 mm et 100 mm.  In general, the optical guiding means comprise a focusing lens, focal length preferably selected from the group consisting of 50 mm, 60 mm and 100 mm.
Le plus souvent, le rayon (ou faisceau) laser est de durée d'impulsion de 100 fs à 50 ns et d'énergie par impulsion de 0,1 à 100 μύ.  Most often, the laser beam (or beam) is of pulse duration from 100 fs to 50 ns and energy per pulse from 0.1 to 100 μύ.
Dans un premier mode de réalisation, le procédé est tel que l'on utilise un laser infrarouge de durée d'impulsion de 100 à 1000 fs, d'énergie par impulsion de 0,1 à 100 μύ, de préférence de 0,1 à 30 μύ, et de longueur d'onde comprise dans une fourchette de 1000 à 1000000 nanomètres. Dans un tel cas, de préférence, le laser est de longueur d'onde 1030 nm.  In a first embodiment, the method is such that an infrared laser with a pulse duration of 100 to 1000 fs, energy per pulse of 0.1 to 100 μύ, preferably 0.1 to 100 μύ, is used. 30 μύ, and wavelength in the range of 1000 to 1,000 nanometers. In such a case, preferably, the laser has a wavelength of 1030 nm.
Dans un second mode de réalisation, le procédé est tel que l'on utilise un laser ultraviolet de durée d'impulsion de 5 à 50 ns, d'énergie par impulsion de 1 à In a second embodiment, the method is such that an ultraviolet laser with a pulse duration of 5 to 50 ns, energy per pulse of 1 to
100 μύ, de préférence 3 μύ à 100 μύ, et de longueur d'onde comprise dans une fourchette de 10 à 380 nanomètres. Dans un tel cas, de préférence, le laser est de longueur d'onde 266 nm. 100 μύ, preferably 3 μύ to 100 μύ, and wavelength in a range of 10 to 380 nanometers. In such a case, preferably, the laser has a wavelength of 266 nm.
Selon une variante, les moyens de guidage laser comprennent au moins un moyen de séparation du rayon laser en plusieurs rayons secondaires de façon à former plusieurs sillons continus à la surface de la forme pharmaceutique solide. De préférence la formation des multiples sillons s'effectue de façon simultanée.  According to a variant, the laser guiding means comprise at least one means for separating the laser beam into a plurality of secondary rays so as to form a plurality of continuous grooves on the surface of the solid pharmaceutical form. Preferably the formation of the multiple grooves takes place simultaneously.
Par « plusieurs », on entend selon l'invention au moins deux.  By "several" is meant according to the invention at least two.
Brève description des figures :  Brief description of the figures:
- la Figure 1 représente schématiquement un système optique formant partie d'un dispositif de marquage laser selon l'invention, et FIG. 1 schematically represents an optical system forming part of a laser marking device according to the invention, and
la Figure 2 représente schématiquement le dispositif de marquage laser selon l'invention comprenant le système optique de la figure 1 .  2 schematically represents the laser marking device according to the invention comprising the optical system of FIG. 1.
La Figure 1 représente schématiquement un système optique 9 formant partie d'un dispositif 1 de marquage laser selon l'invention. Le système optique 9 est constitué des pièces 2, 3, 4, 5, 6, 7 et 8. Figure 1 schematically shows an optical system 9 forming part of a laser marking device 1 according to the invention. The optical system 9 consists of parts 2, 3, 4, 5, 6, 7 and 8.
Une source 2 de rayon laser émet un rayon laser L qui traverse le système optique 9. Ainsi, le rayon laser L traverse une lame h/2 ou lame demi-onde, 3, créant un déphasage valant 180°, c'est-à-dire un retard d'une moitié de longueur d'onde, puis un cube polariseur 4 pour modifier l'énergie par impulsion, ainsi qu'une lame λ/4 ou lame quart d'onde, 5, permettant d'avoir une polarisation circulaire nécessaire à une bonne homogénéité de l'ablation sur les deux axes du balayage laser.  A source 2 of laser beam emits a laser beam L which passes through the optical system 9. Thus, the laser beam L passes through an h / 2 blade or half-wave plate, 3, creating a phase shift of 180 °, that is to say say a delay of half a wavelength, then a polarizer cube 4 to modify the energy per pulse, and a λ / 4 blade or quarter wave plate, 5, to have a polarization circular need for good homogeneity of ablation on both axes of laser scanning.
Le rayon laser ainsi obtenu L' est guidé par deux miroirs, à savoir un miroir 6 à The laser beam thus obtained L 'is guided by two mirrors, namely a mirror 6 to
45°C puis un miroir 7 à 45°C jusqu'à une pièce 8 de focalisation laser munie d'une lentille de focalisation (non représentée) permettant le ciblage et la concentration du rayon laser au point focal. 45 ° C then a mirror 7 at 45 ° C to a laser focussing piece 8 provided with a focusing lens (not shown) for targeting and concentration of the laser beam at the focal point.
La Figure 2 illustre le dispositif 1 de marquage du comprimé C de la Figure 1 . Le dispositif 1 comprend le système optique 9, et permet le marquage d'un comprimé C au moyen d'un rayon laser 1 1 , ciblé et entré, qui est focalisé sur la surface du comprimé C. Comme indiqué ci-dessus, le système optique 9 comprend la source, les éléments optiques et les éléments de focalisation du laser.  Figure 2 illustrates the device 1 for marking the tablet C of Figure 1. The device 1 comprises the optical system 9, and allows the marking of a tablet C by means of a targeted and entered laser beam 11, which is focused on the surface of the tablet C. As indicated above, the system Optical 9 comprises the source, the optical elements and the focusing elements of the laser.
Le comprimé C est présent dans une cavité 10 de forme cylindrique permettant de positionner le comprimé C dans le champ du laser. La cavité 10 appartient à un outillage en aluminium (non représenté) comportant des cavités, par exemple 14 cavités, toutes identiques de diamètre 9,5 mm et de profondeur 6 mm. Cet outillage est apte à être fermé de manière hermétique pour le transport par un capot en plastique transparent.  The tablet C is present in a cylindrical cavity 10 for positioning the tablet C in the laser field. The cavity 10 belongs to an aluminum tool (not shown) having cavities, for example 14 cavities, all identical with a diameter of 9.5 mm and a depth of 6 mm. This tool is able to be closed hermetically for transport by a transparent plastic cover.
Le mouvement relatif de la surface du comprimé et du rayon laser, est ici obtenu par des moyens de déplacement du comprimé liés à l'outillage. En général, la commande et la détection de ces déplacements sont liées à un dispositif de commande, par exemple géré par logiciel, qui analyse aussi les paramètres de la source laser.  The relative movement of the surface of the tablet and the laser beam is here obtained by means of displacement of the tablet related to the tooling. In general, the control and detection of these displacements are linked to a control device, for example managed by software, which also analyzes the parameters of the laser source.
Les exemples qui suivent illustrent l'invention sans pour autant en limiter la portée.  The examples which follow illustrate the invention without limiting its scope.
EXEMPLES  EXAMPLES
Le dispositif 1 selon l'invention a été utilisé pour marquer différents comprimés. La vérification du motif de marquage, qui comprend deux sillons continus fermés à côté l'un de l'autre, a été réalisée par microscope optique. Dans quelques cas le motif de marquage a été caractérisé par microscopie électronique à balayage (MEB). Ainsi, des photos des particules ont été prises au cours des essais, et correspondent à des grossissements x 20 et x 100 pour le microscope optique. The device 1 according to the invention was used to mark different tablets. The verification of the marking pattern, which comprises two continuous grooves closed next to each other, was carried out by optical microscope. In some cases the labeling motif has been characterized by scanning electron microscopy (SEM). Thus, photos of the particles were taken during the tests, and correspond to magnifications x 20 and x 100 for the optical microscope.
Des essais ont été réalisés grâce au dispositif 1 de marquage selon l'invention sur différents comprimés, à savoir :  Tests have been carried out thanks to the marking device 1 according to the invention on different tablets, namely:
un comprimé pelliculé rose foncé : comprimé C1 , de dimension Lxlxh a dark pink film-coated tablet: tablet C1, size LxWxH
15,6x8,1 x4,9 mm, de Rz de 1 1 μηη, et de dureté comprise entre 100 et 160 N; - un comprimé oblong nu, rose clair : comprimé C2, de dimension Lxlxh15.6x8.1 x4.9 mm, Rz of 1 1 μηη, and hardness between 100 and 160 N; - one oblong tablet, light pink: tablet C2, dimension LxWxH
15,5x8,0x4,8 mm, de Rz de 15 μηη, et de dureté comprise entre 100 et 160 N; un comprimé oblong nu blanc : comprimé C3, de dimension Lxlxh15.5x8.0x4.8 mm, Rz 15 μηη, and hardness between 100 and 160 N; a white oblong tablet: tablet C3, size Lxlxh
12,4x6,4x3,6 mm, de Rz de 15 μηη, et de dureté comprise entre 80 et 120 N.12.4x6.4x3.6 mm, with a Rz of 15 μηη, and a hardness between 80 and 120 N.
Les essais réalisés ont consisté à marquer les comprimés en fixant les valeurs de plusieurs paramètres qui sont : la focale de la lentille de focalisation F (qui correspond au diamètre de la lentille utilisée), l'énergie par impulsion E (liée à la puissance P et à la cadence de tir v), la vitesse de balayage (vitesse de déplacement du faisceau sur le laser), et la longueur d'onde λ. Tous ces paramétrages du rayon laser peuvent être résumés en un seul paramètre qui est l'énergie par surface. Dans tous les cas, le but de ces essais de marquage était d'obtenir, pour chaque comprimé, un marquage anti-contrefaçon invisible à l'œil nu, non perceptible au toucher et visible au microscope. Les résultats des différents essais sont synthétisés ci-après. The tests carried out consisted in marking the tablets by fixing the values of several parameters which are: the focal length of the focusing lens F (which corresponds to the diameter of the lens used), the energy per pulse E (linked to the power P and at the firing rate v), the scanning speed (speed of movement of the beam on the laser), and the wavelength λ. All these settings of the laser beam can be summarized in a single parameter which is the energy per area. In all cases, the purpose of these marking tests was to obtain, for each tablet, an anti-counterfeit marking invisible to the naked eye, not perceptible to the touch and visible under the microscope. The results of the various tests are summarized below.
Trois différentes sources de rayons laser ont été utilisées selon ces exemples : - laser S-Pulse HP2 (Amplitude Systèmes), nommé laser I, Three different sources of laser beams were used according to these examples: laser S-Pulse HP 2 (Amplitude Systems), named laser I,
laser S-Pulse (Amplitude Systèmes), nommé laser II, et  S-Pulse laser (Amplitude Systems), named Laser II, and
laser Vanadate Quadruplée, nommé laser III.  Quadrupled Vanadate laser, named Laser III.
Les caractéristiques de ces lasers sont données ci-après :  The characteristics of these lasers are given below:
Laser I :  Laser I:
- Longueur d'onde (λ) : 1030 nm - Wavelength (λ): 1030 nm
Durée d'impulsion : 500 fs  Pulse duration: 500 fs
Energie par impulsion utilisée : 1 - 100 μϋ  Pulse energy used: 1 - 100 μϋ
Lentilles utilisées : f-thêta 100 mm et 60 mm  Lenses used: f-theta 100 mm and 60 mm
Laser II : Longueur d'onde (λ) : 1030 nm Laser II: Wavelength (λ): 1030 nm
Durée d'impulsion : 500 fs Pulse duration: 500 fs
Energie par impulsion utilisée 3,75 - 22,5 Pulse energy used 3.75 - 22.5
Lentilles utilisées : 50mm Lenses used: 50mm
Laser III : Laser III:
Longueur d'onde (λ) : 266 nm  Wavelength (λ): 266 nm
Durée d'impulsion : 25 ns Pulse duration: 25 ns
Energie par impulsion utilisée 3 - 6 Pulse energy used 3 - 6
Lentilles utilisées : Lentille f-thêta 50mm ; Afocal x3 Lenses used: Lens f-theta 50mm; Afocal x3
EXEMPLE 1 : Comprimé pelliculé rose foncé (C1 ) EXAMPLE 1: Dark Pink Film-coated Tablet (C1)
Exemple 1A.  Example 1A.
Un premier essai de marquage d'un comprimé C1 a été réalisé avec le laser I et une focale de 60 mm. Le rayon laser était émis à une cadence de 100 kHz pour une énergie par impulsion de 100 nJ. La vitesse de balayage de la surface de C1 était de 2000 mm/s. L'énergie par surface était de 1 mJ/mm2.  A first marking test of a C1 tablet was performed with the laser I and a focal length of 60 mm. The laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ. The scanning speed of the C1 surface was 2000 mm / s. The energy per area was 1 mJ / mm2.
Cet essai a été réalisé sur un motif comportant deux sillons fermés séparés l'un de l'autre, un sillon de type elliptique et un sillon de type grossièrement elliptique. La distance la plus courte entre ces deux sillons était d'environ 10 μηη.  This test was carried out on a pattern comprising two closed grooves separated from one another, an elliptical-like groove and a groove of roughly elliptical type. The shortest distance between these two furrows was about 10 μηη.
Le motif était de taille 100 x 90 μηη. Ce motif était invisible à l'œil nu. Par microscopie optique avec un agrandissement de 100, il a été possible de visualiser ce motif.  The pattern was of size 100 x 90 μηη. This motif was invisible to the naked eye. By optical microscopy with an enlargement of 100, it was possible to visualize this pattern.
Le pelliculage avait une épaisseur de 50 μηι. Après retrait du pelliculage après essai, par coupe du comprimé à l'aide d'un microtome qui a permis de faire tomber le pelliculage, il a été possible de constater par microscopie électronique à balayage l'intégrité du comprimé et de vérifier que le sillon réalisé par marquage laser n'avait pas traversé la couche de pelliculage.  The filming had a thickness of 50 μηι. After removal of the film coating after the test, by cutting the tablet with a microtome which made it possible to drop the film, it was possible to observe by scanning electron microscopy the integrity of the tablet and to check that the groove made by laser marking had not passed through the film coating layer.
Exemple 1 B. Example 1 B.
Un deuxième essai de marquage d'un comprimé C1 a été réalisé avec le laser A second marking test of a C1 tablet was performed with the laser
III et une focale de 50 mm. Le rayon laser était émis à une cadence de 20 kHz pour une énergie par impulsion de 3000 nJ. La vitesse de balayage de la surface de C1 était de 25 mm/s. L'énergie par surface était de 240 mJ/mm2. III and a focal length of 50 mm. The laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ. The scanning speed of the C1 surface was 25 mm / sec. The energy per surface was 240 mJ / mm 2 .
Un motif complet de taille 190 x 150 μηη a été gravé, comme dans l'exemple 1A.  A complete pattern size 190 x 150 μηη was engraved, as in Example 1A.
Ce motif était invisible à l'œil nu, et parfaitement visible par microscopie optique (« x 100 »).  This motif was invisible to the naked eye, and perfectly visible by optical microscopy ("x 100").
EXEMPLE 2 : Comprimé nu rose clair (C2) EXAMPLE 2: Light Pink Nude Tablet (C2)
Exemple 2A. Example 2A.
Un premier essai de marquage d'un comprimé C2 a été réalisé avec le laser I et une focale de 60 mm. Le rayon laser était émis à une cadence de 100 kHz pour une énergie par impulsion de 100 nJ. La vitesse de balayage de la surface de C1 était de 200 mm/s. L'énergie par surface était de 5 mJ/mm2. A first marking test of a C2 tablet was performed with the laser I and a focal length of 60 mm. The laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ. The scanning speed of the surface of C1 was 200 mm / s. The energy per area was 5 mJ / mm 2.
Un motif complet de taille 200 x 180 μιη a été gravé, comme dans l'exemple A complete pattern of size 200 x 180 μιη has been engraved, as in the example
1A. 1A.
Ce motif était invisible à l'œil nu, et parfaitement visible par microscopie optique (« x 100 »).  This motif was invisible to the naked eye, and perfectly visible by optical microscopy ("x 100").
Exemple 2B. Example 2B.
Un deuxième essai de marquage 5 d'un comprimé C2 a été réalisé avec le laser III et une focale de 50 mm. Le rayon laser était émis à une cadence de 20 kHz pour une énergie par impulsion de 3000 nJ. La vitesse de balayage de la surface de C1 était de 25 mm/s. L'énergie par surface était de 240 mJ/mm2.  A second marking test of a C2 tablet was performed with the laser III and a focal length of 50 mm. The laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ. The scanning speed of the C1 surface was 25 mm / sec. The energy per surface was 240 mJ / mm 2.
Un motif complet de taille 190 x 150 μηη a été gravé, comme dans l'exemple A complete pattern of size 190 x 150 μηη has been engraved, as in the example
1A. 1A.
Les résultats obtenus par microscopie optique (« x 100 ») montrent une taille de motif visible alors qu'elle n'est pas visible à l'œil nu. On a tout particulièrement noté que, pour le laser III, le motif était encore plus net qu'avec le laser I.  The results obtained by optical microscopy ("x 100") show a visible pattern size while it is not visible to the naked eye. It was particularly noted that for the laser III, the pattern was even clearer than with the laser I.
EXEMPLE 3 : Comprimé nu blanc non pelliculé (C3) Exemple 3A. EXAMPLE 3: White uncoated (C3) white tablet Example 3A.
Un premier essai de marquage d'un comprimé C3 a été réalisé avec le laser III et une focale de 50 mm. Le rayon laser était émis à une cadence de 20 kHz pour une énergie par impulsion de 3000 nJ. La vitesse de balayage de la surface de C1 était de 50 mm/s. L'énergie par surface était de 120 mJ/mm2.  A first marking test of a C3 tablet was performed with the laser III and a focal length of 50 mm. The laser beam was emitted at a rate of 20 kHz for a pulse energy of 3000 nJ. The scanning speed of the C1 surface was 50 mm / sec. The area energy was 120 mJ / mm 2.
Le motif gravé complet était de taille 190 x 150 μηη, comme dans l'exemple 1A. The complete engraved pattern was 190 x 150 μηη, as in Example 1A.
Les résultats obtenus par le microscope optique avec un grossissement de 100 ont montré un motif visible alors qu'il n'était pas visible à l'œil nu. The results obtained by the optical microscope with a magnification of 100 showed a visible pattern while it was not visible to the naked eye.
Exemple 3B. Example 3B.
Un deuxième essai de marquage d'un comprimé C3 a été réalisé avec le laser A second C3 tablet marking test was performed with the laser
Il et une focale de 60 mm. Le rayon laser était émis à une cadence de 100 kHz pour une énergie par impulsion de 100 nJ. La vitesse de balayage de la surface de C1 était de 200 mm/s. L'énergie par surface était de 2,5 mJ/mm2. He and a focal length of 60 mm. The laser beam was emitted at a rate of 100 kHz for a pulse energy of 100 nJ. The scanning speed of the C1 surface was 200 mm / sec. The energy per area was 2.5 mJ / mm2.
Le motif gravé complet était de taille 200 x 180 μηη, comme dans l'exemple 1A. Le motif, non visible à l'œil nu, était visible en microscopie optique avec un grossissement de 100, la netteté étant meilleure dans le cas du laser III que dans le cas du laser II. The complete engraved pattern was of size 200 x 180 μηη, as in Example 1A. The pattern, not visible to the naked eye, was visible in optical microscopy with a magnification of 100, the sharpness being better in the case of the laser III than in the case of the laser II.
Enfin, des tests de répétabilité ont été effectués en utilisant le laser I et une focale de 60 mm, à raison de 10 comprimés par essai, pour les exemples 1A, 2A Finally, repeatability tests were performed using the laser I and a focal length of 60 mm, at a rate of 10 tablets per test, for Examples 1A, 2A.
(la seule différence résidant dans la vitesse de balayage de 200 mm/s dans le cas de l'essai répété) et 3A. Il a été observé une grande répétabilité. (the only difference is the sweep rate of 200 mm / s in the repeat test) and 3A. It has been observed a great repeatability.
Dans tous les cas, dans un cadre industriel, le temps de marquage moyen correspond à environ 80 ms. Ce temps de marquage moyen comprend généralement le temps dû au traitement des informations par le logiciel de marquage et le temps dû au marquage en lui-même. Ceci pourrait être aisément optimisé dans le cadre de l'invention en utilisant un logiciel dédié à un motif particulier ou en multipliant le nombre de faisceaux lasers par un système optique démultipliant le faisceau initial.  In all cases, in an industrial setting, the average marking time is about 80 ms. This average marking time generally includes the time due to the processing of the information by the marking software and the time due to the marking itself. This could easily be optimized within the scope of the invention by using software dedicated to a particular pattern or by multiplying the number of laser beams by an optical system that multiplies the initial beam.

Claims

REVENDICATIONS
1 . Forme pharmaceutique solide marquée comprenant au moins un sillon continu marquant sa surface, ledit sillon étant de profondeur comprise dans une fourchette de 20 μηη à 50 μηι. 1. A marked solid pharmaceutical form comprising at least one continuous groove marking its surface, said groove being of depth lying in the range of 20 μηη to 50 μηι.
Forme pharmaceutique selon la revendication 1 , telle que le sillon présente une largeur comprise dans une fourchette de 5 μηη à 120 μηη, de préférence de 10 μηη à 100 μηη. Pharmaceutical form according to claim 1, such that the groove has a width in a range of 5 μηη to 120 μηη, preferably 10 μηη to 100 μηη.
Forme pharmaceutique selon l'une des revendications 1 à 2, telle que le sillon forme une ligne continue fermée. Pharmaceutical form according to one of claims 1 to 2, such that the groove forms a closed continuous line.
4. Forme pharmaceutique selon l'une des revendications 1 à 3, telle que le sillon est de longueur comprise dans une fourchette de 250 μηη à 3 mm, de préférence de 250 μηη à 500 μηι. 4. Pharmaceutical form according to one of claims 1 to 3, such that the groove is of length in a range of 250 μηη to 3 mm, preferably from 250 μηη to 500 μηι.
Forme pharmaceutique selon l'une des revendications 1 à 4, telle que la surface de la forme pharmaceutique a une profondeur de rugosité moyenne mesurée par la norme IS04287 :1998, comprise dans une fourchette de 10 μηη à 40 μηι, de préférence de 20 μηη à 40 μηι. Pharmaceutical form according to one of claims 1 to 4, such that the surface of the pharmaceutical form has a mean depth of roughness measured by the standard IS04287: 1998, in a range of 10 μηη to 40 μηι, preferably 20 μηη at 40 μηι.
Forme pharmaceutique selon l'une des revendications 1 à 5, telle qu'elle comprend au moins deux sillons formant chacun une ligne continue fermée. Pharmaceutical form according to one of claims 1 to 5, such that it comprises at least two grooves each forming a closed continuous line.
Forme pharmaceutique selon l'une des revendications 1 à 6, telle que le sillon s'inscrit dans un carré de côté compris dans une fourchette de 100 μηη à 250 μηι, de préférence de 200 μηη à 250 μηι. Pharmaceutical form according to one of claims 1 to 6, such that the groove is in a side square within a range of 100 μηη to 250 μηι, preferably from 200 μηη to 250 μηι.
Procédé de marquage d'au moins une forme pharmaceutique solide selon l'une des revendications 1 à 7, ledit procédé comprenant la formation d'au moins un sillon par ablation de la surface de la forme solide au moyen d'un rayon laser, ledit procédé étant tel que l'ablation laser est effectuée avec une énergie laser comprise dans une fourchette de 0, 1 mJ/mm2 à 500 mJ/mm2, de préférence dans une fourchette de 0,1 mJ/mm2 à 250 mJ/mm2. A method of labeling at least one solid dosage form according to one of claims 1 to 7, said method comprising forming at least one groove by ablating the surface of the solid form by means of a laser beam, said method being such that laser ablation is performed with a laser energy in the range of 0.1 mJ / mm 2 to 500 mJ / mm 2 , preferably in a range of 0.1 mJ / mm 2 to 250 mJ / mm 2 .
9. Procédé de marquage selon la revendication 8, ledit procédé comprenant la fourniture d'une source de rayon laser, la fourniture de moyens de guidage optique du rayon laser jusqu'à la surface de la forme, la fourniture de moyens de déplacement relatif entre la forme et le rayon laser, et la réalisation d'un sillon continu en surface de la forme au moyen d'ablation laser par le rayon laser et au moyen du déplacement relatif de la surface et du rayon laser. 9. A method of marking according to claim 8, said method comprising providing a source of laser beam, providing means for optically guiding the laser beam to the surface of the form, providing relative displacement means between shape and laser beam, and producing a continuous groove on the surface of the shape by means of laser ablation by the laser beam and by means of the relative displacement of the surface and the laser beam.
10. Procédé selon l'une des revendications 8 ou 9, tel que les moyens de guidage optique comprennent une lentille de focalisation, de focale de préférence choisie dans le groupe formé par 50 mm, 60 mm et 100 mm. 10. Method according to one of claims 8 or 9, such that the optical guide means comprise a focussing lens, focal length preferably selected from the group formed by 50 mm, 60 mm and 100 mm.
1 1 . Procédé selon l'une des revendications 8 à 10, tel que l'on utilise un laser infrarouge de durée d'impulsion de 100 à 1000 fs, d'énergie par impulsion de 0,1 à 100 μύ, de préférence de 0,1 à 30 μύ, et de longueur d'onde comprise dans une fourchette de 1000 à 1000000 nanomètres. 1 1. Method according to one of claims 8 to 10, such as using an infrared laser with pulse duration of 100 to 1000 fs, energy per pulse of 0.1 to 100 μύ, preferably 0.1 at 30 μύ, and having a wavelength in the range of 1000 to 1,000 nanometers.
12. Procédé selon la revendication 1 1 , tel que l'on utilise un laser de longueur d'onde de 1030 nm. 12. The method of claim 1 1, such that a laser with a wavelength of 1030 nm is used.
13. Procédé selon l'une des revendications 8 à 12, tel que l'on utilise un laser ultraviolet de durée d'impulsion de 5 à 50 ns, d'énergie par impulsion de 1 à 100 μύ, de préférence 3 μύ à 100 μύ, et de longueur d'onde comprise dans une fourchette de 10 à 380 nanomètres. 13. Method according to one of claims 8 to 12, such that one uses an ultraviolet laser with a pulse duration of 5 to 50 ns, energy per pulse of 1 to 100 μύ, preferably 3 μύ to 100 μύ. μύ, and wavelength in the range of 10 to 380 nanometers.
14. Procédé selon la revendication 13, tel que l'on utilise un laser de longueur d'onde de 266 nm. The method of claim 13, wherein a 266 nm wavelength laser is used.
15. Procédé selon l'une des revendications 8 à 14, tel que les moyens de guidage laser comprennent au moins un moyen de séparation du rayon laser en plusieurs rayons secondaires de façon à former, de préférence de façon simultanée, plusieurs sillons continus à la surface de la forme pharmaceutique. 15. Method according to one of claims 8 to 14, such that the laser guiding means comprise at least one means for separating the laser beam into a plurality of secondary rays so as to form, preferably simultaneously, several continuous grooves on the surface of the pharmaceutical form.
EP11802465.2A 2010-11-03 2011-11-03 Marked solid pharmaceutical form, and method for the production thereof by means of laser marking Withdrawn EP2635246A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1059063A FR2966731B1 (en) 2010-11-03 2010-11-03 SOLID PHARMACEUTICAL FORM MARKERED AND METHOD OF MANUFACTURING BY LASER MARKING
PCT/FR2011/052565 WO2012059693A1 (en) 2010-11-03 2011-11-03 Marked solid pharmaceutical form, and method for the production thereof by means of laser marking

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AR (1) AR083682A1 (en)
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WO (1) WO2012059693A1 (en)

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WO2012059693A1 (en) 2012-05-10
TW201231091A (en) 2012-08-01
FR2966731A1 (en) 2012-05-04
AR083682A1 (en) 2013-03-13
FR2966731B1 (en) 2013-04-26
JP2013541580A (en) 2013-11-14
US20130244002A1 (en) 2013-09-19

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